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Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

2021; BioMed Central; Volume: 28; Issue: 1 Linguagem: Inglês

10.1186/s12929-020-00703-5

1423-0127

Ioannis P. Trougakos, Κimon Stamatelopoulos, Evangelos Terpos, Ourania E. Tsitsilonis, Evmorfia Aivalioti, Dimitrios Paraskevis, Efstathios Kastritis, George N. Pavlakis, Meletios Α. Dimopoulos,

Long-Term Effects of COVID-19

Abstract Background Gaining further insights into SARS-CoV-2 routes of infection and the underlying pathobiology of COVID-19 will support the design of rational treatments targeting the life cycle of the virus and/or the adverse effects (e.g., multi-organ collapse) that are triggered by COVID-19-mediated adult respiratory distress syndrome (ARDS) and/or other pathologies. Main body COVID-19 is a two-phase disease being marked by ( phase 1 ) increased virus transmission and infection rates due to the wide expression of the main infection-related ACE2 , TMPRSS2 and CTSB/L human genes in tissues of the respiratory and gastrointestinal tract, as well as by ( phase 2 ) host- and probably sex- and/or age-specific uncontrolled inflammatory immune responses which drive hyper-cytokinemia, aggressive inflammation and (due to broad organotropism of SARS-CoV-2) collateral tissue damage and systemic failure likely because of imbalanced ACE/ANGII/AT1R and ACE2/ANG(1–7)/MASR axes signaling. Conclusion Here we discuss SARS-CoV-2 life cycle and a number of approaches aiming to suppress viral infection rates or propagation; increase virus antigen presentation in order to activate a robust and durable adaptive immune response from the host, and/or mitigate the ARDS-related “cytokine storm” and collateral tissue damage that triggers the severe life-threatening complications of COVID-19.